Evaluation of the initial response in clinical trials efforts for COVID-19 in Brazil

Abstract

Objective: To describe the methodological characteristics and good research practices of the intervention studies for COVID-19 developed in Brazil in the first months of the pandemic. Method: A review in the CONEP-COVID bulletin (05/28/2020) and the International Clinical Trials Registry Platform, ClinicalTrials.gov, ReBEC was conducted to identify drug-type, biological therapy or vaccine intervention studies registered in Brazil. The studies were evaluated for methodological characteristics and power for different magnitudes of effect. Results: 62 studies were included, 55 identified on the CONEP website and seven on a registration database. Several interventions are being tested: chloroquine/hydroxychloroquine, azithromycin, plasma convalescent, tocilizumab, sarilumab, eculizumab, vaccine, corticoids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, lopinavir/ritonavir, etc. By May 2020, 22 research protocols were published in a protocol registry database, 82% were randomized clinical trials and 59% had adequate control group. However, 59% were not masked and only 24% included patients with positive test with diagnostic accuracy. Most of the studies would have power >80% just to identify large effect sizes. In a prospective follow-up, until July 21st/2020, 60% of the studies available at CONEP were not registered in the ICTRP/ReBEC/ClinicalTrials platforms. Conclusion: The interventions evaluated during the Brazilian research response reflect international initiatives, but with a different distribution, a larger proportion of studies asseessed hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.